ACE inhibitors in myocardial infarction

In general, patients initiated on ACE inhibitors in myocardial infarction (MI) have demonstrated a reduction in overall mortality by about 20% to 30%. This benefit is most profound in patients with symptomatic congestive heart failure and their therapy should be continued indefinitely.

The renin-angiotensin-aldosterone system (RAAS) regulates aldosterone release in the body via the action of angiotensin II on angiotensin I receptors.

Angiotensin II by itself is also a potent vasoconstrictor (even more than norepinephrine), leading to hypertension. Its other harmful effects include the promotion of atherosclerosis and hypertrophic changes in the blood vessels and left ventricle. Angiotensin-converting enzyme (ACE) inhibitors, by blocking the conversion of angiotensin I to angiotensin II, are believed to attenuate ventricular dilatation and remodeling.

Furthermore, ACE inhibitors block the degradation of bradykinin, which is thought to have antihypertensive effects. The accumulation of bradykinin is believed to be the cause of the chronic cough associated with use of ACE inhibitors. Angiotensin II receptor blockers (ARBs), on the other hand, work further downstream in the RAAS by blocking angiotensin II at the receptor site.

However, therapy in patients without evidence of left ventricular dysfunction may be ceased after 4 to 6 weeks. These patients should then be re-evaluated in 4 to 6 months to reassess ventricular function.

Patients who are intolerant to ACE inhibitors in myocardial infarction (because of severe cough, etc.) may take an ARB as a suitable alternative. Valsartan was recently compared with captopril and found to be as effective at reducing mortality, heart failure hospitalizations, and reinfarction.

Of interest to clinicians is that patients taking chronic ACE inhibitor therapy have demonstrated circulating angiotensin II levels similar to that prior to initiating therapy.

This ACE escape syndrome is incompletely understood but thought to be associated with other synthetic pathways for angiotensin II. Hence, maximal blockade of the RAAS would encompass blocking both the formation of angiotensin II and action of angiotensin II on the angiotensin I receptor.
In congestive heart failure patients, this combination therapy has been shown to decrease the incidence of hospitalizations for heart failure. However, combination therapy has yet to show any survival benefit in patients during myocardial infarction, with or without heart failure.

Barring hypotension (systolic blood pressure <100 mm Hg), treatment with an ACE inhibitors in myocardial infarction or ARB should be commenced on the first post-MI day (as early as the first 12 hours). Therapy should be initiated only after the routine recommended administration of thrombolytic therapy, aspirin, and beta-blockers.

Captopril offers the advantage of being the drug whose use within the first 24 hours has been best studied (SAVE and ISIS-4 trial). However, various ACE inhibitors including lisinopril (GISSI-3 trial), ramipril (AIRE trial), and trandolapril (TRACE trial) have also received FDA approval for treatment of heart failure after myocardial infarction. Enalapril (CONSENSUS-II trial) and zofenopril (SMILE trial), though not currently FDA approved for treatment during myocardial infarction, are also felt to be equivalent in their beneficial effect on mortality.

Currently, valsartan (VALIANT trial) is the only ARB that has been FDA approved for use during myocardial infarction.

The most common cause for discontinuing ACE inhibitors in myocardial infarction in the acute peri-MI period is hypotension. This is unusual, but it can occur in up to 2% of heart failure patients who have undergone vigorous intravascular depletion from diuretic use.

Intravascular volume depletion can in turn cause decreased renal perfusion and azotemia. In general, renal insufficiency Cr >2.5 mg/dL is a contraindication in initiating or continuing therapy, as is renal artery stenosis. Hyperkalemia (K >5.5 mEq/mL) can occur as a result of decreased aldosterone levels. Other rare adverse reactions include dry cough, rash, and angioedema.


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